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High mobility group box-1 protects against Aflatoxin G1-induced pulmonary epithelial cell damage in the lung inflammatory environment.
- Source :
-
Toxicology Letters . Oct2020, Vol. 331, p92-101. 10p. - Publication Year :
- 2020
-
Abstract
- • Upregulation of HMGB1 was observed in AFG 1 -induced lung inflamed tissues. • AFG 1 -induced TNF-α-dependent inflammation regulates HMGB1 upregulation in vivo. • AFG 1 enhanced cytosolic translocation and secretion of HMGB1 in Beas-2b cells. • The addition of extracellular soluble HMGB1 protected AFG 1 -induced DNA damage. • Blockade endogenous HMGB1 by siRNA significantly enhanced AFG 1 -induced damage. Aflatoxin G 1 (AFG 1) is a member of the carcinogenic aflatoxin family. Our previous studies indicated that oral administration of AFG 1 caused tumor necrosis factor (TNF)-α-dependent inflammation that enhanced oxidative DNA damage in alveolar epithelial cells, which may be related to AFG 1 -induced lung carcinogenesis. High mobility group box-1 (HMGB1) is a nuclear DNA-binding protein; the intracellular and extracellular roles of HMGB1 have been shown to contribute to DNA repair and sterile inflammation. The role of HMGB1 in DNA damage in an aflatoxin-induced lung inflammatory environment was investigated in this study. Upregulation of HMGB1, TLR2, and RAGE was observed in AFG 1 -induced lung inflamed tissues and adenocarcinoma. Blocking AFG 1 -induced inflammation by neutralization of TNF-α inhibited the upregulation of HMGB1 in mouse lung tissues, suggesting that AFG 1 -induced TNF-α-dependent inflammation regulated HMGB1 expression. In the in vitro human pulmonary epithelial cell line model, Beas-2b, AFG 1 directly enhanced the cytosolic translocation of HMGB1 and its extracellular secretion. The addition of extracellular soluble HMGB1 protected AFG 1 -induced DNA damage through the TLR2/NF-κB pathway in Beas-2b cells. In addition, blockade of endogenous HMGB1 by siRNA significantly enhanced AFG 1 -induced damage. Thus, our findings showed that both extracellularly-released and nuclear and cytosolic HMGB1 could protect the cell from AFG 1 -induced cell damage in a TNF-α-dependent lung inflammatory environment. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 03784274
- Volume :
- 331
- Database :
- Academic Search Index
- Journal :
- Toxicology Letters
- Publication Type :
- Academic Journal
- Accession number :
- 144460097
- Full Text :
- https://doi.org/10.1016/j.toxlet.2020.05.013